p53 and c-Jun Functionally Synergize in the Regulation of the DNA Repair Gene hMSH2 in Response to UV*

The tumor suppresser protein p53 is critical for guarding the genome from incorporation of damaged DNA (Lane, D. P. (1992) Nature 358, 15–16). A relevant stress that activates p53 function is UV light (Noda, A., Toma-Aiba, Y., and Fujiwara, Y. (2000) Oncogene 19, 21–31). Another well known component of the mammalian UV response is the transcription factor c-Jun (Angel, P., and Karin, M. (1991) Biochim. Biophys. Acta 1072, 129–157). We show here that upon UV irradiation p53 activates transcription of the human mismatch repair geneMSH2. Interestingly, this up-regulation critically depends on functional interaction with c-Jun. Hence, the synergistic interaction of a proto-oncogene with a tumor suppresser gene is required for the regulation of the mammalian stress response through activation of expression of MSH2.

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